This proposal aims at training an M.D. clinical researcher in the new areas of: 1) the epigenetics of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD); and 2) bioinformatics for genome- wide data analysis. This training will be accomplished through a project that will utilize an already identified unique cohot of >1,300 female military personnel with comprehensive trauma history and mental health diagnosis and treatment baseline data. The goal will be to identify epigenetic biomarkers of trauma and PTSD and MDD susceptibility. Unfortunately, female military personnel are at high risk for sexual trauma during their service, with up to 30% suffering from this experience. Among these women, over 25% develop PTSD and more than 14% develop MDD. While genetic susceptibility plays a role in the development of these disorders, epigenetic modifications induced by trauma exposure likely play a critical role in illness susceptibility. With the advent o next-generation genome-wide assessment approaches, relatively low-cost, high-throughput methods to study DNA methylation are now available. While these technologies have made enormous leaps forward and can now provide us with a torrent of data, the methods for making sense of the data are still catching up. While disease-based genome-wide DNA methylation measurement can turn up hundreds of thousands of epigenetic marks in cases, it takes great statistical and bioinformatic sophistication to determine which of them plays an etiologic role in illness. The applicant proposes to learn the critical techniques for handling genome- wide DNA methylation data. This will be accomplished in part through pursuit of a Master's degree in bioinformatics. He will also be trained in psychiatric epigenetics by his primary mentor, who is an established expert in this new field. This project will be accomplished through the following specific aims: 1) To determine whether DNA methylation (DNAm) levels within particular genes are correlated with a history of exposure to sexual assault in the military (SAIM) among women; 2) To determine whether DNAm levels within particular genes are correlated with the likelihood of developing PTSD and MDD, given exposure to SAIM; and 3) To determine, in this exploratory aim, whether DNAm levels within particular genes are correlated with the likelihood of treatment response in PTSD and MDD, given exposure to SAIM. This proposal will allow for the development of the applicant as an expert in bringing together bioinformatics and epigenetics in the study of PTSD and MDD. Results will provide new insights into biomarkers that could be of value in assessing people at risk for PTSD and MDD, and potentially in identifying those for whom preventive interventions should be initiated. In addition, this training will provide the applicant with a set of tools that will be widely applicable to the study of epigenetic marks acros complex psychiatric illnesses.